The purpose of this project is to study the effects of central stimulant agents and stress on the neuronal activities of both central and peripheral catecholaminergic nervous system: 1) Cocaine-induced behavioral and neurochemical effects resemble those of amphetamine. Both cocaine and amphetamine caused an increase in the level of catecholamines in cerebrospinal fluid and in plasma. The increase in release of dopamine after amphetamine resulted in an increase in striatal 3-methoxytyramine rather than homovanilic acid. The results indicate that amphetamine acts directly on the nerve terminal to induce release whereas cocaine acts to increase neuronal firing by a local anesthetic effect on brain inhibitory neurons. The inhibition of re-uptake by both drugs further augments their in vivo catecholamine releasing actions. 2) Plasma levels of catecholamines were used as an index for activities of the peripheral sympathetic nervous system. It was found that plasma catecholamines depend upon the degree of stress. Resting levels of plasma catecholamine in conscious, undisturbed rats were less than 0.5 ng/ml. Plasma catecholamines were increased 2- to 4-fold in young rats (3 or 8 months old) but not in aged rats (28 months old). The exact mechanism for the lack of significant sympathetic responsiveness to stress in the aged rats remains to be investigated.